{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:20:43Z","timestamp":1777987243366,"version":"3.51.4"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Camerino to M.U.","award":["grant FAR-2019"],"award-info":[{"award-number":["grant FAR-2019"]}]},{"name":"University of Camerino to M.U.","award":["grant 202213"],"award-info":[{"award-number":["grant 202213"]}]},{"name":"Hetzler Foundation to N.C.","award":["grant FAR-2019"],"award-info":[{"award-number":["grant FAR-2019"]}]},{"name":"Hetzler Foundation to N.C.","award":["grant 202213"],"award-info":[{"award-number":["grant 202213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The neuropeptide S (NPS) is the endogenous ligand of the NPS receptor (NPSR). The NPSR is widely expressed in brain regions that process emotional and affective behavior. NPS possesses a unique physio-pharmacological profile, being anxiolytic and promoting arousal at the same time. Intracerebroventricular NPS decreased alcohol consumption in alcohol-preferring rats with no effect in non-preferring control animals. This outcome is most probably linked to the anxiolytic properties of NPS, since alcohol preference is often associated with high levels of basal anxiety and intense stress-reactivity. In addition, NPSR mRNA was overexpressed during ethanol withdrawal and the anxiolytic-like effects of NPS were increased in rodents with a history of alcohol dependence. In line with these preclinical findings, a polymorphism of the NPSR gene was associated with anxiety traits contributing to alcohol use disorders in humans. NPS also potentiated the reinstatement of cocaine and ethanol seeking induced by drug-paired environmental stimuli and the blockade of NPSR reduced reinstatement of cocaine-seeking. Altogether, the work conducted so far indicates the NPS\/NPSR system as a potential target to develop new treatments for alcohol and cocaine abuse. An NPSR agonist would be indicated to help individuals to quit alcohol consumption and to alleviate withdrawal syndrome, while NPSR antagonists would be indicated to prevent relapse to alcohol- and cocaine-seeking behavior.<\/jats:p>","DOI":"10.3390\/ph15070800","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:07:02Z","timestamp":1656374822000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Role for Neuropeptide S in Alcohol and Cocaine Seeking"],"prefix":"10.3390","volume":"15","author":[{"given":"Nazzareno","family":"Cannella","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Borruto","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Petrella","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-1206","authenticated-orcid":false,"given":"Maria Vittoria","family":"Micioni Di Bonaventura","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Soverchia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-828X","authenticated-orcid":false,"given":"Carlo","family":"Cifani","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-196X","authenticated-orcid":false,"given":"Sara","family":"De Carlo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-4814","authenticated-orcid":false,"given":"Esi","family":"Domi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-2483","authenticated-orcid":false,"given":"Massimo","family":"Ubaldi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/cne.22603","article-title":"Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain","volume":"519","author":"Liu","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/cne.21159","article-title":"Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain","volume":"500","author":"Xu","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.neuron.2004.08.005","article-title":"Neuropeptide S: A neuropeptide promoting arousal and anxiolytic-like effects","volume":"43","author":"Xu","year":"2004","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/bjp.2008.96","article-title":"Neuropeptide S is a stimulatory anxiolytic agent: A behavioural study in mice","volume":"154","author":"Rizzi","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.biopsych.2010.05.039","article-title":"Assessment of the neuropeptide S system in anxiety disorders","volume":"68","author":"Donner","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.neuropharm.2016.03.054","article-title":"Neuropeptide S reduces fear and avoidance of con-specifics induced by social fear conditioning and social defeat, respectively","volume":"108","author":"Zoicas","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neuron.2008.07.002","article-title":"Neuropeptide S-mediated control of fear expression and extinction: Role of intercalated GABAergic neurons in the amygdala","volume":"59","author":"Jungling","year":"2008","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meis, S., Bergado-Acosta, J.R., Yanagawa, Y., Obata, K., Stork, O., and Munsch, T. (2008). Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002695"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1124\/jpet.105.093427","article-title":"Pharmacological characterization of human and murine neuropeptide s receptor variants","volume":"315","author":"Reinscheid","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/mp.2010.79","article-title":"A neuropeptide S receptor variant associated with overinterpretation of fear reactions: A potential neurogenetic basis for catastrophizing","volume":"15","author":"Raczka","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.pnpbp.2007.06.026","article-title":"Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit\/hyperactivity disorder","volume":"31","author":"Okamura","year":"2007","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1038\/npp.2011.73","article-title":"Neuropeptide-S (NPS) receptor genotype modulates basolateral amygdala responsiveness to aversive stimuli","volume":"36","author":"Dannlowski","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102029","DOI":"10.1016\/j.nicl.2019.102029","article-title":"Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls","volume":"24","author":"Gechter","year":"2019","journal-title":"Neuroimage Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/mp.2010.81","article-title":"Neuropeptide S receptor gene\u2014converging evidence for a role in panic disorder","volume":"16","author":"Domschke","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1111\/j.1460-9568.2009.06948.x","article-title":"The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S","volume":"30","author":"Fedeli","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Botticelli, L., Micioni Di Bonaventura, E., Ubaldi, M., Ciccocioppo, R., Cifani, C., and Micioni Di Bonaventura, M.V. (2021). The Neural Network of Neuropeptide S (NPS): Implications in Food Intake and Gastrointestinal Functions. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040293"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3510","DOI":"10.1210\/en.2005-1280","article-title":"Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake","volume":"147","author":"Smith","year":"2006","journal-title":"Endocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.biopsych.2015.04.021","article-title":"Activation of Hypocretin-1\/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S","volume":"79","author":"Ubaldi","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1038\/npp.2009.37","article-title":"Persistent increase of alcohol-seeking evoked by neuropeptide S: An effect mediated by the hypothalamic hypocretin system","volume":"34","author":"Cannella","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19567","DOI":"10.1073\/pnas.1004100107","article-title":"Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system","volume":"107","author":"Kallupi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.neuroscience.2012.01.022","article-title":"Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons","volume":"207","author":"Zhao","year":"2012","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1523\/JNEUROSCI.5256-08.2009","article-title":"Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice","volume":"29","author":"Paneda","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1113\/jphysiol.2011.226423","article-title":"Activation of neuropeptide S-expressing neurons in the locus coeruleus by corticotropin-releasing factor","volume":"590","author":"Jungling","year":"2012","journal-title":"J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12929-019-0590-1","article-title":"Neuropeptide S-initiated sequential cascade mediated by OX1, NK1, mGlu5 and CB1 receptors: A pivotal role in stress-induced analgesia","volume":"27","author":"Lee","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1038\/npp.2015.125","article-title":"Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval","volume":"40","author":"Jungling","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eabg9045","DOI":"10.1126\/sciadv.abg9045","article-title":"A neural substrate of compulsive alcohol use","volume":"7","author":"Domi","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nature09553","article-title":"Genetic dissection of an amygdala microcircuit that gates conditioned fear","volume":"468","author":"Haubensak","year":"2010","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1016\/j.pain.2014.04.026","article-title":"Persistent nociception induces anxiety-like behavior in rodents: Role of endogenous neuropeptide S","volume":"155","author":"Zhang","year":"2014","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.npep.2017.11.004","article-title":"The ventromedial hypothalamic nucleus plays an important role in anxiolytic-like effect of neuropeptide S","volume":"67","author":"Jiang","year":"2018","journal-title":"Neuropeptides"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"zsz189","DOI":"10.1093\/sleep\/zsz189","article-title":"Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons","volume":"43","author":"Chauveau","year":"2020","journal-title":"Sleep"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13009","DOI":"10.1111\/adb.13009","article-title":"Stress-induced escalation of alcohol self-administration, anxiety-like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats","volume":"26","author":"Barchiesi","year":"2021","journal-title":"Addict. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12214","DOI":"10.1523\/JNEUROSCI.2161-17.2017","article-title":"Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis","volume":"37","author":"Grund","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s00213-008-1080-4","article-title":"Pharmacology of neuropeptide S in mice: Therapeutic relevance to anxiety disorders","volume":"197","author":"Leonard","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neulet.2009.03.023","article-title":"Neuropeptide S facilitates spatial memory and mitigates spatial memory impairment induced by N-methyl-D-aspartate receptor antagonist in mice","volume":"455","author":"Han","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1111\/ejn.13613","article-title":"Neuropeptide S precursor knockout mice display memory and arousal deficits","volume":"46","author":"Liu","year":"2017","journal-title":"Eur. J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.peptides.2007.01.008","article-title":"Phylogenetic appearance of neuropeptide S precursor proteins in tetrapods","volume":"28","author":"Reinscheid","year":"2007","journal-title":"Peptides"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/adb.12149","article-title":"Neuropeptide S receptor gene variant and environment: Contribution to alcohol use disorders and alcohol consumption","volume":"20","author":"Laas","year":"2015","journal-title":"Addict. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/0269881112472562","article-title":"A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study","volume":"28","author":"Laas","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"827","DOI":"10.2165\/11591790-000000000-00000","article-title":"Obsessive-compulsive disorder, impulse control disorders and drug addiction: Common features and potential treatments","volume":"71","author":"Fontenelle","year":"2011","journal-title":"Drugs"},{"key":"ref_40","first-page":"541","article-title":"Interaction of the neuropeptide S receptor gene Asn(1)(0)(7)Ile variant and environment: Contribution to affective and anxiety disorders, and suicidal behaviour","volume":"17","author":"Laas","year":"2014","journal-title":"Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/cne.22606","article-title":"Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry","volume":"519","author":"Clark","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3389\/fnana.2015.00126","article-title":"Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons","volume":"9","author":"Adori","year":"2015","journal-title":"Front. Neuroanat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.neuroscience.2010.10.020","article-title":"Immunohistochemical localization of the neuropeptide S receptor in the rat central nervous system","volume":"172","author":"Leonard","year":"2011","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Meis, S., Stork, O., and Munsch, T. (2011). Neuropeptide S-mediated facilitation of synaptic transmission enforces subthreshold theta oscillations within the lateral amygdala. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018020"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1152\/jn.00874.2012","article-title":"Neuropeptide S: A novel regulator of pain-related amygdala plasticity and behaviors","volume":"110","author":"Ren","year":"2013","journal-title":"J. Neurophysiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/npp.2011.317","article-title":"Intranasally administered neuropeptide S (NPS) exerts anxiolytic effects following internalization into NPS receptor-expressing neurons","volume":"37","author":"Ionescu","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Dine, J., Ionescu, I.A., Stepan, J., Yen, Y.C., Holsboer, F., Landgraf, R., Eder, M., and Schmidt, U. (2013). Identification of a role for the ventral hippocampus in neuropeptide S-elicited anxiolysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060219"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.expneurol.2019.02.015","article-title":"Central neuropeptide-S treatment improves neurofunctions of 6-OHDA-induced Parkinsonian rats","volume":"317","author":"Bulbul","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.peptides.2010.02.006","article-title":"Microinjection of neuropeptide S into the rat ventral tegmental area induces hyperactivity and increases extracellular levels of dopamine metabolites in the nucleus accumbens shell","volume":"31","author":"Mochizuki","year":"2010","journal-title":"Peptides"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1471-4159.2010.06947.x","article-title":"Neuropeptide S stimulates dopaminergic neurotransmission in the medial prefrontal cortex","volume":"115","author":"Si","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1476-5381.2009.00163.x","article-title":"Neuropeptide S selectively inhibits the release of 5-HT and noradrenaline from mouse frontal cortex nerve endings","volume":"157","author":"Raiteri","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.peptides.2015.07.024","article-title":"Neuropeptide S Increases locomotion activity through corticotropin-releasing factor receptor 1 in substantia nigra of mice","volume":"71","author":"Li","year":"2015","journal-title":"Peptides"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbr.2014.03.002","article-title":"Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice","volume":"266","author":"Didonet","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.peptides.2008.10.004","article-title":"Neuropeptide S inhibits the acquisition and the expression of conditioned place preference to morphine in mice","volume":"30","author":"Li","year":"2009","journal-title":"Peptides"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1038\/npp.2012.102","article-title":"Chronic ethanol potentiates the effect of neuropeptide s in the basolateral amygdala and shows increased anxiolytic and anti-depressive effects","volume":"37","author":"Enquist","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.pneurobio.2012.09.005","article-title":"The role of the neuropeptide S system in addiction: Focus on its interaction with the CRF and hypocretin\/orexin neurotransmission","volume":"100","author":"Cannella","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejphar.2011.02.009","article-title":"Intraventricular administration of neuropeptide S has reward-like effects","volume":"658","author":"Cao","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.neuropharm.2013.02.002","article-title":"Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or Abeta(1)(-)(4)(2) in mice novel object and object location recognition tasks","volume":"70","author":"Han","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.neuint.2013.02.003","article-title":"Neuropeptide S inhibits release of 5-HT and glycine in mouse amygdala and frontal\/prefrontal cortex through activation of the neuropeptide S receptor","volume":"62","author":"Gardella","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/npp.2010.207","article-title":"Neuropeptide S enhances memory during the consolidation phase and interacts with noradrenergic systems in the brain","volume":"36","author":"Okamura","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.nlm.2013.10.010","article-title":"Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation","volume":"107","author":"Han","year":"2014","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.npep.2017.04.005","article-title":"Neuropeptide S increases motor activity and thermogenesis in the rat through sympathetic activation","volume":"65","author":"Ensho","year":"2017","journal-title":"Neuropeptides"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1385\/ENDO:30:1:75","article-title":"Centrally administered neuropeptide S activates orexin-containing neurons in the hypothalamus and stimulates feeding in rats","volume":"30","author":"Niimi","year":"2006","journal-title":"Endocrine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1001\/archpsyc.61.8.807","article-title":"Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions","volume":"61","author":"Grant","year":"2004","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.biopsych.2010.06.015","article-title":"Drug addiction endophenotypes: Impulsive versus sensation-seeking personality traits","volume":"68","author":"Ersche","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/j.1360-0443.2008.02223.x","article-title":"Impulsivity, age of first alcohol use and substance use disorders among male adolescents: A population based case-control study","volume":"103","author":"Bassani","year":"2008","journal-title":"Addiction"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1111\/j.1530-0277.2008.00713.x","article-title":"The effects of neuropeptide S on ethanol drinking and other related behaviors in alcohol-preferring and -nonpreferring rats","volume":"32","author":"Henderson","year":"2008","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1007\/s00213-016-4333-7","article-title":"Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats","volume":"233","author":"Cannella","year":"2016","journal-title":"Psychopharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.peptides.2010.10.018","article-title":"Effect of neuropeptide S receptor antagonists and partial agonists on palatable food consumption in the rat","volume":"32","author":"Cifani","year":"2011","journal-title":"Peptides"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.bbrc.2005.05.029","article-title":"Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats","volume":"332","author":"Beck","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1369-1600.2006.00032.x","article-title":"Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: An animal model to study the neurobiology of alcoholism","volume":"11","author":"Ciccocioppo","year":"2006","journal-title":"Addict. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Dine, J., Ionescu, I.A., Avrabos, C., Yen, Y.C., Holsboer, F., Landgraf, R., Schmidt, U., and Eder, M. (2015). Intranasally applied neuropeptide S shifts a high-anxiety electrophysiological endophenotype in the ventral hippocampus towards a \u201cnormal\u201d-anxiety one. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120272"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.neuropharm.2011.08.016","article-title":"Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: Social versus non-social effects","volume":"62","author":"Lukas","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1016\/j.peptides.2008.08.014","article-title":"Anxiolytic-like effect of neuropeptide S in the rat defensive burying","volume":"29","author":"Vitale","year":"2008","journal-title":"Peptides"},{"key":"ref_75","first-page":"375","article-title":"Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: A genetic animal model of depression","volume":"15","author":"Wegener","year":"2012","journal-title":"Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108446","DOI":"10.1016\/j.neuropharm.2020.108446","article-title":"Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation?","volume":"186","author":"Borruto","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0741-8329(93)90046-Q","article-title":"Comparison of alcohol-preferring (P) and nonpreferring (NP) rats on tests of anxiety and for the anxiolytic effects of ethanol","volume":"10","author":"Stewart","year":"1993","journal-title":"Alcohol"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fnbeh.2019.00003","article-title":"Sub-dimensions of Alcohol Use Disorder in Alcohol Preferring and Non-preferring Rats, a Comparative Study","volume":"13","author":"Domi","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1530-0277.1991.tb00552.x","article-title":"Individual mood profiles in alcohol withdrawal","volume":"15","author":"Bokstrom","year":"1991","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0741-8329(85)90123-5","article-title":"Hyperventilation, anxiety, craving for alcohol: A subacute alcohol withdrawal syndrome","volume":"2","author":"Roelofs","year":"1985","journal-title":"Alcohol"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1530-0277.2009.01070.x","article-title":"Neuropeptide S receptor gene expression in alcohol withdrawal and protracted abstinence in postdependent rats","volume":"34","author":"Ruggeri","year":"2010","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1523\/JNEUROSCI.4985-06.2007","article-title":"3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo [1,2-b]pyridazine: A novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism","volume":"27","author":"Gehlert","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.biopsych.2008.02.004","article-title":"Dysregulation of nociceptin\/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat","volume":"64","author":"Economidou","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/adb.12157","article-title":"MT-7716, a potent NOP receptor agonist, preferentially reduces ethanol seeking and reinforcement in post-dependent rats","volume":"20","author":"Teshima","year":"2015","journal-title":"Addict. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/adb.12671","article-title":"phMRI, neurochemical and behavioral responses to psychostimulants distinguishing genetically selected alcohol-preferring from genetically heterogenous rats","volume":"24","author":"Bifone","year":"2019","journal-title":"Addict. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1523\/JNEUROSCI.4764-13.2015","article-title":"Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity","volume":"35","author":"Slattery","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10132","DOI":"10.1523\/JNEUROSCI.4742-12.2013","article-title":"A novel brain penetrant NPS receptor antagonist, NCGC00185684, blocks alcohol-induced ERK-phosphorylation in the central amygdala and decreases operant alcohol self-administration in rats","volume":"33","author":"Thorsell","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/026988119801200103","article-title":"Conditioning factors in drug abuse: Can they explain compulsion?","volume":"12","author":"Childress","year":"1998","journal-title":"J. Psychopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/jnc.15343","article-title":"Neurobiology of alcohol seeking behavior","volume":"157","author":"Domi","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.brainres.2016.10.018","article-title":"Orexin\/hypocretin-1 receptor antagonism reduces ethanol self-administration and reinstatement selectively in highly-motivated rats","volume":"1654","author":"Moorman","year":"2017","journal-title":"Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/sj.bjp.0706789","article-title":"The orexin system regulates alcohol-seeking in rats","volume":"148","author":"Lawrence","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1111\/j.1530-0277.2007.00510.x","article-title":"Orexigenic peptides and alcohol intake: Differential effects of orexin, galanin, and ghrelin","volume":"31","author":"Schneider","year":"2007","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Srinivasan, S., Simms, J.A., Nielsen, C.K., Lieske, S.P., Bito-Onon, J.J., Yi, H., Hopf, F.W., Bonci, A., and Bartlett, S.E. (2012). The dual orexin\/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administration. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044726"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1111\/bph.15210","article-title":"Nicotine increases alcohol self-administration in male rats via a mu-opioid mechanism within the mesolimbic pathway","volume":"177","author":"Domi","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/alcalc\/agaa139","article-title":"Targeting the Opioid Receptors: A Promising Therapeutic Avenue for Treatment in \u201cHeavy Drinking Smokers\u201d","volume":"56","author":"Domi","year":"2021","journal-title":"Alcohol Alcohol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1124\/jpet.107.135103","article-title":"Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor","volume":"325","author":"Okamura","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00213-012-2910-y","article-title":"Hypothalamic neuropeptide S receptor blockade decreases discriminative cue-induced reinstatement of cocaine seeking in the rat","volume":"226","author":"Kallupi","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1016\/j.bmcl.2010.04.143","article-title":"Synthesis and evaluation of a new series of Neuropeptide S receptor antagonists","volume":"20","author":"Melamed","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1016\/j.bmcl.2008.05.098","article-title":"Identifying structural features on 1,1-diphenyl-hexahydro-oxazolo[3,4-a]pyrazin-3-ones critical for Neuropeptide S antagonist activity","volume":"18","author":"Zhang","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.pbb.2012.09.003","article-title":"Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats","volume":"103","author":"Schmoutz","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ejphar.2014.09.006","article-title":"Effects of the neuropeptide S receptor antagonist RTI-118 on abuse-related facilitation of intracranial self-stimulation produced by cocaine and methylenedioxypyrovalerone (MDPV) in rats","volume":"743","author":"Bonano","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e12971","DOI":"10.1111\/adb.12971","article-title":"Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid","volume":"26","author":"Chou","year":"2021","journal-title":"Addict. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"12199","DOI":"10.1038\/ncomms12199","article-title":"Orexins contribute to restraint stress-induced cocaine relapse by endocannabinoid-mediated disinhibition of dopaminergic neurons","volume":"7","author":"Tung","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.brainres.2009.10.068","article-title":"Convergent actions of orexin\/hypocretin and CRF on dopamine neurons: Emerging players in addiction","volume":"1314","author":"Borgland","year":"2010","journal-title":"Brain Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"11439","DOI":"10.1523\/JNEUROSCI.3459-04.2004","article-title":"Interaction between the corticotropin-releasing factor system and hypocretins (orexins): A novel circuit mediating stress response","volume":"24","author":"Yamanaka","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.regpep.2003.12.014","article-title":"Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: Possible involvement of central orexins on stress-activated central CRF neurons","volume":"118","author":"Sakamoto","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1046\/j.1365-2826.2001.00655.x","article-title":"Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats","volume":"13","author":"Wilson","year":"2001","journal-title":"J. Neuroendocrinol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1523\/JNEUROSCI.23-01-00007.2003","article-title":"Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins\/hypocretins","volume":"23","author":"Korotkova","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.neuron.2006.01.016","article-title":"Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine","volume":"49","author":"Borgland","year":"2006","journal-title":"Neuron"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1111\/j.1460-9568.2006.04792.x","article-title":"Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat","volume":"23","author":"Korotkova","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1523\/JNEUROSCI.0955-05.2005","article-title":"Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: A role in stress-induced relapse to drug seeking","volume":"25","author":"Wang","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1523\/JNEUROSCI.2761-05.2006","article-title":"Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine","volume":"26","author":"Narita","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1111\/j.1460-9568.2007.05403.x","article-title":"Implication of protein kinase C in the orexin-induced elevation of extracellular dopamine levels and its rewarding effect","volume":"25","author":"Narita","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.biopsych.2009.01.018","article-title":"Reinstatement of cocaine seeking by hypocretin (orexin) in the ventral tegmental area: Independence from the local corticotropin-releasing factor network","volume":"65","author":"Wang","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuropharm.2017.03.001","article-title":"Identification of the first biased NPS receptor agonist that retains anxiolytic and memory promoting effects with reduced levels of locomotor stimulation","volume":"118","author":"Clark","year":"2017","journal-title":"Neuropharmacology"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/7\/800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:10Z","timestamp":1760139550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/7\/800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":115,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ph15070800"],"URL":"https:\/\/doi.org\/10.3390\/ph15070800","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}